McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Int J Neuropsychopharmacol. 2013 Mar;16(2):289-99. doi: 10.1017/S1461145712000363. Epub 2012 May 9.
The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 and SYN3) with alternative splicing resulting in a number of variants with various levels of homology. These genes have been postulated to play significant roles in several neuropsychiatric disorders, including bipolar disorder, schizophrenia and epilepsy. Epigenetic regulatory mechanisms, such as histone modifications in gene regulatory regions, have also been proposed to play a role in a number of psychiatric disorders, including bipolar disorder and major depressive disorder. One of the best characterized histone modifications is histone 3 lysine 4 tri-methylation (H3K4me3), an epigenetic mark shown to be highly enriched at transcriptional start sites and associated with active transcription. In the present study we have quantified the expression of transcript variants of the three synapsin genes and investigated their relationship to H3K4me3 promoter enrichment in post-mortem brain samples. We found that histone modification marks were significantly increased in bipolar disorder and major depression and this effect was correlated with significant increases in gene expression. Our findings suggest that synapsin dysregulation in mood disorders is mediated in part by epigenetic regulatory mechanisms.
神经元磷酸化蛋白突触结合蛋白家族由三个基因（SYN1、SYN2 和 SYN3）组成，这些基因通过选择性剪接产生了许多具有不同同源性水平的变体。这些基因被认为在多种神经精神疾病中发挥重要作用，包括双相情感障碍、精神分裂症和癫痫。表观遗传调控机制，如基因调控区域的组蛋白修饰，也被认为在多种精神疾病中发挥作用，包括双相情感障碍和重度抑郁症。组蛋白修饰中研究最充分的一种是组蛋白 3 赖氨酸 4 三甲基化（H3K4me3），这是一种在转录起始位点高度富集的表观遗传标记，与活跃转录有关。在本研究中，我们定量了三个突触结合蛋白基因的转录变体的表达，并研究了它们与死后脑组织中 H3K4me3 启动子富集的关系。我们发现，在双相情感障碍和重度抑郁症中，组蛋白修饰标记显著增加，并且这种效应与基因表达的显著增加相关。我们的研究结果表明，在心境障碍中，突触结合蛋白的失调部分是由表观遗传调控机制介导的。
